Prediction of Malignant Transformation of Oral Leukoplakia Using a MAGE-A-based Immunoscore

NCT03975322 | Recruiting

• 1 other identifier: 1.4
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Oral squamous cell carcinomas (OSCC) is among the most common malignancies worldwide. Early detection and prevention of OSCC is thought to have the highest potential to reduce morbidity and mortality. In prevention, the main focus is on precancerous lesions, especially oral leukoplakia (OLP), as up to 67% of OSCC arise on the basis of OLP. The determination of the transformation risk of OLP by histological determination of the degree of dysplasia is unreliable. A promising marker for the timely development of a OSCC is the detection of antigens of the MAGE-A gene family. The special feature of MAGE-A is that they can be detected in 93% of all OSCC and in approx. 85% of OLP that transform to OSCC. The detection of MAGE-A could also indicate changes in the immunological environment that occur prior to malignant OLP transformation and could be used for immunotherapies. Aim of this study is to investigate MAGE-A as a predictive marker for the malignant transformation of OLP in the setting of a prospective, multicenter study and to establish it as a diagnostic parameter in addition to classical histology. In addition, the association of MAGE-A expression with the occurrence of immunological changes in OLP will be investigated in order to evaluate the possibility of minimally invasive immunotherapy of OLP. The study is intended to include 500 biopsies of non-selected patients with OLP from university institutions and private practices. The follow-up should be at least 3 years, whereby it is examined whether an OSCC on the basis of the original OLP developed. After three years, an interim evaluation of the results with statistical evaluation will be carried out. In order to ensure that the course of the disease is monitored for at least three years for all OLPs, an extension of the monitoring period to 5 years is planned. The study could establish a routine diagnostic parameter to supplement the histo-morphological diagnosis of OLP and evaluate the possibility of immunotherapy of OLP.

Conditions

Oral Leukoplakia; Oral Leukoplakia of Tongue; Oral Leukoplakia of Gingiva; Oral Lichen Planus

Keywords

OLP; oral cancer; OSCC; oral squamous cell carcinoma

Outcome Measures

Primary Outcomes (3)

• Dependence of malignant transformation on a MAGE-A based immunoscore

  Association of OLP malignant transformation with a MAGE-A based immunoscore. Into this score, the following immunohistochemical and molecular biological parameters determined in biopsies will be integrated: * MAGE-A expression * Macrophage infiltration and polarization (CD68, CD163) * T cell infiltration (CD3, CD8) * Altered expression of immune checkpoints and TLR receptors (PD-L1, PD-L2, TLR7) These parameters will be aggregated to an immunoscore

  2 years

• Dependence of malignant transformation on a MAGE-A based immunoscore

  Association of OLP malignant transformation with a MAGE-A based immunoscore. Into this score, the following immunohistochemical and molecular biological parameters determined in biopsies will be integrated: * MAGE-A expression * Macrophage infiltration and polarization (CD68, CD163) * T cell infiltration (CD3, CD8) * Altered expression of immune checkpoints and TLR receptors (PD-L1, PD-L2, TLR7) These parameters will be aggregated to an immunoscore

  3 years

• Dependence of malignant transformation on a MAGE-A based immunoscore

  Association of OLP malignant transformation with a MAGE-A based immunoscore. Into this score, the following immunohistochemical and molecular biological parameters determined in biopsies will be integrated: * MAGE-A expression * Macrophage infiltration and polarization (CD68, CD163) * T cell infiltration (CD3, CD8) * Altered expression of immune checkpoints and TLR receptors (PD-L1, PD-L2, TLR7) These parameters will be aggregated to an immunoscore

  5 years

Secondary Outcomes (6)

• Frequency of malignant transformation

  2 years

• Frequency of malignant transformation

  3 years

• Frequency of malignant transformation

  5 years

• Dependence of malignant transformation on dysplasia

  2 years

• Dependence of malignant transformation on dysplasia

  3 years

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with clinically proven leukoplakia (OLP) of the oral cavity (whitish, non-wipeable oral mucosa changes that cannot be attributed to any disease) are to be included in the study.

You may qualify if:

• Adults, consenting male or female patients
• Age 18 - 80 years
• Diagnosis of one or more leukoplakia of the oral cavity
• including
• leukoplakia associated wit lichen planus OR
• leukoplakia associated with diseases of the immune system or immunosuppression OR
• leukoplakia associated with a malignoma of other sites (except oral cavity) in the anamnesis
• Existing consent to participation in the study after clarification has been given

You may not qualify if:

• clinical evidence of invasive carcinoma of the oral cavity OR
• carcinoma of the oral cavity in the anamnesis OR
• patients unable to give informed consent OR
• rejection of the patient

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (1)

Universitätsklinikum Erlangen, FAU Erlangen-Nürnberg

Erlangen, 91054, Germany

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

paraffin specimens and RNAlater specimens

MeSH Terms

Conditions

Leukoplakia, Oral; Lichen Planus, Oral; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Leukoplakia; Precancerous Conditions; Mouth Diseases; Stomatognathic Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Lichen Planus; Lichenoid Eruptions; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Manuel Weber, MD, DMD

  Maxillofacial Surgery Erlangen

  STUDY CHAIR

• Falk Wehrhan, MD, DMD

  Maxillofacial Surgery Erlangen

  STUDY CHAIR

• Jutta Ries, PhD

  Maxillofacial Surgery Erlangen

  STUDY CHAIR

Central Study Contacts

Manuel Weber, MD, DMD

CONTACT

0049 9131 85 43749; manuel.weber@uk-erlangen.de

Falk Wehrhan, MD, DMD

CONTACT

0049 9131 85 43731; falk.wehrhan@uk-erlangen.de

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. med. Dr. med. dent. Manuel Weber, MD, DMD, Principal Investigator

Study Record Dates

• First Submitted: May 27, 2019
• First Posted: June 5, 2019
• Study Start: December 1, 2019
• Primary Completion: December 30, 2024
• Study Completion (Estimated): December 30, 2026
• Last Updated: December 3, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)